Multimodality CT/SPECT Evaluation of Micelle Drug Carriers for Treatment of Breast Tumors

摘要

Polymer micelles are nanoscale drug delivery systems that have the potential to improve breast tumor treatment. Micelles can increase the half- life and solubility of drugs, as is the case with beta-lapachone (beta-lap), a novel anticancer agent which is bioactivated by the enzyme NQO1, found overexpressed in tumors. They can also be fitted with tumor-specific ligands, and can be tracked in vivo through incorporation of an imaging moiety. The ultimate goal of the study was to develop beta-lap PEG-PLA micelles as novel nanotherapeutics for the treatment of breast tumors. Quantum dots (QD) were incorporated into micelles for purposes of image trackability. Micelles were characterized using 1H-NMR, TEM, and DLS. The in vitro and in vivo antitumor efficacy of the micelles was also examined. Beta-lap micelles were found to be small in size, and showed adequate cell-killing potential in vitro. In vivo studies showed that the micelles suppressed tumor growth for approximately 2 months, with minimal toxicity. QDs were successfully incorporated into micelles, yielding micelles of small size that retained fluorescence. Cell lines treated in vitro with the QD-micelles demonstrated slow and continuous uptake of micelles, found accumulated in the cytoplasm. Future studies involve the addition of a cRGD ligand to the surface of micelles to increase cellular uptake and yield multifunctional micelles.